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Related Concept Videos

Notch Signaling Pathway03:14

Notch Signaling Pathway

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The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
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Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

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Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
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Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
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Related Experiment Video

Updated: Feb 7, 2026

Murine Model of Leukemia Relapse to Induction Chemotherapy for Acute Lymphoblastic Leukemia
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Notch in Leukemia.

Anna C McCarter1, Qing Wang2, Mark Chiang3

  • 1Cell and Molecular Biology Program, University of Michigan, Ann Arbor, MI, USA.

Advances in Experimental Medicine and Biology
|July 22, 2018
PubMed
Summary
This summary is machine-generated.

Notch pathway activation drives lymphoid cancers through various mechanisms. New strategies targeting Notch

Keywords:
AKTChronic lymphocytic leukemiaMYCNotchT-cell acute lymphoblastic leukemia

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Area of Science:

  • Oncology
  • Molecular Biology
  • Hematology

Background:

  • The Notch signaling pathway is frequently activated in lymphoid malignancies.
  • Activation occurs via ligand-dependent or ligand-independent mechanisms, differing between T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) and chronic lymphocytic leukemia (CLL).

Purpose of the Study:

  • To review Notch activation mechanisms in lymphoid cancers.
  • To discuss the role of Notch in lymphoid malignancy development and maintenance.
  • To explore challenges and emerging strategies for targeting the Notch pathway in cancer therapy.

Main Methods:

  • Review of existing literature on Notch signaling in lymphoid malignancies.
  • Analysis of mechanisms of Notch activation, including NRR mutations and PEST domain deletions.
  • Discussion of clinical trial outcomes and novel therapeutic approaches.

Main Results:

  • Ligand-independent Notch activation predominates in T-ALL via NRR mutations.
  • Ligand-dependent Notch activation occurs in CLL.
  • PEST domain mutations impair intracellular Notch (ICN) degradation.
  • Clinical trials of pan-Notch inhibitors face toxicity and resistance issues.

Conclusions:

  • Understanding Notch activation nuances is crucial for developing effective therapies.
  • Targeting specific Notch interactions or downstream pathways offers promise.
  • New strategies focus on the "nuclear context" to achieve selective cancer cell targeting and minimize side effects.